A heritable disorder of lithium transport in erythrocytes of a subpopulation of manic-depressive patients.

The in vivo RBC/plasma Li+ ratio is determined by the equilibrium between Li+ influx (ouabain-sensitive Na+-K+ pump and ouabain-insensitive leakage pathways) and Li+ efflux (phloretin-sensitive Li+-Na+ counterflow). A study of RBC Li+ transport via these pathways showed that a deficiency of Li+-Na+ counterflow was responsible for the high in vivo ratio (1:1) observed in a manic patient. This defect was related to an alteration in the membrane Na+ exchange system and was under genetic control. The level of counterflow before lithium therapy was an excellent predictor (r = .88) of the in vivo Li+ ratio and was deficient in approximately one-fourth of manic-depressive patients but not in controls, schizophrenics, or unipolar depressed patients.